Mr. B, age 66, was diagnosed 30 years ago with type I bipolar disorder and has type 2 diabetes, hypertension, alcohol abuse disorder, and cardiac disease. After repeated suicide attempts and hospitalizations in the past, he has been stable for 20 years on lithium, 600 mg bid, and nortriptyline, 50 mg at bedtime. He has had intermittent mania with little evidence of depression.

Two years ago, Mr. B called a local clinic to report that an intruder had him “holed up.” His speech was pressured and garbled, and his thoughts were tangential, irrational, and markedly paranoid. A clinic psychiatrist called Mr. B’s son, who said his father “built a bomb shelter” because “trolls and little people” were out to kill him. A family member called police, and Mr. B was brought to the ER and admitted for treatment.

A hospital psychiatrist stopped lithium in light of Mr. B’s history of cardiac problems and because the psychiatrist considered the medication ineffective, even though serum lithium was only 0.03 mEq/L. The psychiatrist then started:

divalproex at 500 mg bid, titrated over 1 week to 500 mg each morning and 1,000 mg at bed-time to reach serum valproate of 80 mEq/L

quetiapine at 200 mg at bedtime, titrated over 1 week to 400 mg at bedtime.

Mr. B was still manic, paranoid, and hallucinating 1 week later, yet was discharged after he convinced the county hearing officer that he had recovered.

Two weeks later, Mr. B is brought to another psychiatric hospital, where a psychiatrist restarts unknown dosages of lithium, risperidone, and nortriptyline. From there, he is transferred to our in-patient unit. At presentation, he claims he has been drinking and that members of a drug cartel have recruited him. He says he has been skipping medications because he is “unclear which drugs to take.”

We stop lithium and restart divalproex, 500 mg each morning and 1,500 mg at bedtime, to try to treat his mania without causing cognitive problems.

We stop risperidone because of his hypotension and nortriptyline because it was not working, and restart quetiapine, 600 mg at bedtime, for his paranoia. He remains paranoid 1 week later but his mania improves, so we discharge him on the above regimen. We urge him to take his medications and follow up with his outpatient psychiatrist 1 week later.

Divorced, Mr. B lives alone with no family nearby. His son comes in from out of town to help him resettle after discharge, then leaves the next day.

Several months later, Mr. B’s paranoia returns. He is not taking his medications because “the doctors took away my lithium and these new drugs don’t work.” He tells staff he is a martial arts expert and has purchased 7 cars in recent weeks. We restart lithium at 600 mg bid; serum lithium reaches 1.1 mEq/L, but his mania persists. After 5 days, we add aripiprazole, 15 mg/d.

Nearly 2 weeks after admission, a county hearing officer recommends discharging Mr. B despite his severe mania and paranoia. We release him on the above regimen, arrange appointments with his outpatient psychiatrist and primary care physician, and urge medication adherence. We schedule a blood test 3 days after discharge to check serum lithium, but Mr. B does not keep the appointment.

The authors’ observations

Suspect delirium after rapid onset of mania or paranoia in any patient. Also consider dementia and cognitive deficits in older adults, although Mr. B’s symptoms resembled those of previous manic episodes. Although Mr. B’s psychosis was more severe than before, his case underscores the importance of a thorough patient history.

Late-life bipolar disorder. Little is known about diagnosing and treating bipolar disorder (BPD) in older patients. Gaps in empiric knowledge can confound diagnosis, treatment, and outcome. Also, patients age ≥65 with BPD often have severe medical illness and are difficult to treat.1

Older patients’ symptoms usually match DSM-IV-TR criteria for BPD; their response to treatment mirrors that of younger adults.3

Secondary cause. When an older patient’s mania has atypical features or doesn’t respond to conventional treatment, look for a nonpsychiatric process such as a general medical condition or substance abuse (see possible medical causes with this article at www.currentpsychiatry.com). Order laboratory and other tests as clinical suspicion warrants.

Cognitive deficits secondary to BPD can occur at any age and be persistent or progressive,4 although Depp et al1 found more-severe impairment in older patients. Cognitive impairment can endure after successful BPD treatment, although acute treatment might improve cognition in older patients.5

Dementia. Cognitive deficits that accompany mania in older adults could suggest dementia, which usually develops over years and is preceded by cognitive changes without manic-type symptoms. By contrast, bipolar mania emerges more abruptly and is accompanied by affective symptoms. Agitation and psychosis—both symptoms of late-stage dementia—can be early signs of geriatric BPD.2

Delirium. Restlessness, irritability, aggression, and changes in affect can accompany delirium, especially the hyperactive or hyperalert types. Symptoms of anxiety, depression, fear, and loose or tangential thinking also are common.

Mania shares some of these features but typically presents with an abnormally and persistently elevated or irritable mood lasting ≥1 week, usually without prominent cognitive impairment.6 Mania can also include:

By contrast, delirium is marked by waxing and waning consciousness and changes in cognition, such as disorientation and confusion.6

Frontal lobe lesions. Decreased prefrontal executive control could underlie mania’s cognitive and emotional symptoms. Decreased right rostral and orbital prefrontal cortex activation has been associated with impaired planning, judgment, and insight, as well as inappropriate conduct.7

Table

Clinical features of geriatric bipolar disorder (BPD)

Psychotic features (delusions, hallucinations)

Mean prevalence of 64% (range 20% to 85%) is similar to that of mixed-age groups; paranoia might be more prevalent

Family history

High rates of psychiatric disorders (“affective disorder” in most studies) reported in 10 studies

Compared with younger adults with BPD, older patients:

show longer latency from first depression to mania onset

might be more likely to relapse into depression after mania

might have less-intense mania

are hospitalized longer, possibly because of greater medical comorbidity

have less comorbid substance abuse and more-prominent age-associated morphologic abnormalities on neuroimaging2

Compared with late-life schizophrenia, late-life BPD patients show:

more depressive symptoms

fewer positive and negative symptoms

greater community living and relationship skills, with similar activities of daily living

Several months later, Mr. B presents with severe depression and continued medication nonadherence. He complains of hypersomnia, poor appetite, anhedonia, amotivation, and a leaden-like paresis in his hands and feet.

We readmit Mr. B to the psychiatric unit. He avoids contact with others, has lost 18 lbs over 6 weeks, and suffers hypotension caused by poor hydration before admission. Three weeks later, he complains that ants are crawling around his room and into his mouth.

Noncontrast brain CT shows no abnormalities. Laboratory tests performed at admission show a subtherapeutic lithium level (0.03 mEq/L), unremarkable thyroid panel, and normal B12 and folate, so we begin to rule out a medical cause for his psychiatric symptoms.

The authors’ observations

Check for these and other possible causes of depressive symptoms in older patients with a history of BPD. Mr. B’s depression likely resulted from multiple causes, including medical disease, functional impairment, loss of social and family contacts, and substance abuse—all late-life predictors of depression. BPD also predisposed him to depression.

Bipolar depression. Despite its profound morbidity and mortality, bipolar depression remains a mystery, especially in the elderly. Mr. B’s depression emerged after he was free of depressive symptoms for more than 20 years.

Some researchers believe that compared with other depressions, bipolar depression has a more acute onset, marked psychomotor retardation, and lessened response to antidepressants.6,8 Kraepelin associated bipolar depression with lethargy, mental slowing, and hypersomnia, whereas agitation and insomnia signal unipolar depression.9

To differentiate bipolar from unipolar or secondary depression in older patients, watch for:

secondary manias, for which underlying causes must be determined and treated if possible.

Medication-induced depression. Medications can cause depressive symptoms (see Related resources), but identifying an offending agent without an obvious chronologic relationship can be difficult, especially in older patients who are taking numerous medications.9

Depression caused by medication might be limited to somatic complaints such as fatigue or tiredness,9 and often lacks features seen with mood disorders such as depressed mood, anhedonia, guilt, and diminished interest in activities. Mr. B’s anhedonia and amotivation suggest his depression was not medication-induced.10

Disease-induced depression. Medical comorbidities are common among older persons with mood disorders and can complicate treatment response and outcome. Physical disease can cause or worsen depression:11

What defines vascular depression has been debated. Watch for clinical or laboratory evidence of vascular disease, depression, and neuropsychological impairment.13

Treatment: searching for evidence

Two days after admission, Mr. B is transferred to the ICU after suffering severe hypoglycemia and showing signs of medically induced delirium. Elevated creatinine (1.7 mg/dL) indicates acute renal failure, which could be related to his elevated serum lithium (1.7 mEq/L). Acting on the internist’s advice, the consulting psychiatrist stops lithium and restarts valproate, 500 mg bid.

Mr. B becomes medically stable after 3 days, mostly through acute IV hydration and by withholding oral diabetes medications, which normalizes his blood sugar. He is transferred back to the psychiatry unit. We try lithium again at 300 mg bid, but creatinine and serum lithium quickly rise.

An early refill request for psychostimulants for your college-age patient

﻿Mr. R, age 18, who has been taking amphetamine/dextroamphetamine, 10 mg/d, twice a day, for attention-deficit/hyperactivity disorder since he was age 10, comes to see you shortly after beginning college asking to refill earlier than usual. He says his symptoms are worse since beginning college and he is finding it difficult to focus in class and keep up with the heavy course work. He says he has been taking an extra 10 mg when he “needs the extra boost.” He asks for an early refill and increased dosage. How do you proceed?

Switch to an extended release formulation and increase the dosage to 30 mg/d

Switch to lisdexamfetamine, 30 mg/d

Prescribe amphetamine/dextroamphetamine, 10 mg, on an as-needed basis

Tell Mr. R to take his current prescription as prescribed and discuss the dangers of stimulant abuse. Reassess his symptoms at the next visit.